Electrostatic/electrostrictive actuation of elastomer structures using compliant electrodes

ABSTRACT

A valve structure comprises an elastomeric block formed with first and second microfabricated recesses separated by a membrane portion of the elastomeric block. The valve is actuated by positioning a compliant electrode on a first side of the first recess proximate to and in physical communication with the membrane. Where the valve is to be electrostatically actuated, a second electrode is positioned on a second side of the first recess opposite the first side. Application of a potential difference across the electrodes causes the compliant electrode and the membrane to be attracted into the flow channel. Where the valve is to be electrostrictively actuated, a second electrode is positioned on the same side of the recess as the compliant electrode. Application of a potential difference across the electrodes causes the electrodes to be attracted such that elastomer membrane portion material between them is compressed and bows into the flow channel. Either of the electrostrictively or the electrostatically-actuated valve structures may include an electrically-conducting fluid in the second recess to serve as the compliant electrode.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. patent application Ser. No.10/232,997, entitled “ELECTROSTATIC/ELECTROSTRICTIVE ACTUATION OFELASTOMER STRUCTURES USING COMPLIANT ELECTRODES,” filed Aug. 29, 2002 byMarc Unger (“the '997 application”), the entire disclosure of which isincorporated herein by reference for all purposes. The '997 applicationis a nonprovisional of, and claims the benefit of the filing date of,each of the following provisional patent applications: Ser. No.60/316,343 and Ser. No. 60/316,431, both filed Aug. 30, 2001. Theseprovisional patent applications are hereby incorporated by reference.

BACKGROUND OF THE INVENTION

PCT Application WO 01/01025 (“the '025 application), published Jan. 4,2001, describes in detail manufacture and operation of pump and valvesystems microfabricated from elastomer materials. The '025 applicationis hereby incorporated by reference in its entirety.

FIG. 7B shows a cross-sectional view of one embodiment of a non-actuatedvalve structure described in the '025 application. The valve structurecomprises control recess 32 oriented orthogonal relative to underlyingflow channel 30. Control recess 32 is separated from flow channel 30 byelastomer membrane 25. Membrane 25 is created from the same elastomericmaterial in which control recess 32 is formed. The floor of flow channel30 may be formed from a rigid non-elastomeric substrate 14 such asglass, or may be formed from an underlying elastomer layer.

During operation, membrane 25 experiences an actuation force that causesit to deflect into and thereby obstruct a flow of material through theunderlying flow channel. This is shown in FIG. 7H, which is across-sectional view of the valve structure of FIG. 7B in an actuatedstate. As described in detail in the '025 application, the actuationforce displacing membrane 25 into the flow channel can take many forms,including but not limited to elevated pneumatic or hydraulic pressurewithin control recess 32 relative to flow channel 30.

Given the large number of potential applications for elastomericmicrofluidic handling systems described in the '025 application, it isseen that alternative structures and methods for actuation aredesirable.

SUMMARY OF THE INVENTION

A valve structure comprises an elastomeric block formed with first andsecond microfabricated recesses separated by a membrane portion of theelastomeric block. The valve is actuated by positioning a compliantelectrode on a first side of the first recess proximate to and inphysical communication with the membrane. Where the valve is to beelectrostatically actuated, a second electrode is positioned on a secondside of the first recess opposite the first side. Application of apotential difference across the electrodes causes the compliantelectrode and the membrane to be attracted into the flow channel. Wherethe valve is to be electrostrictively actuated, a second electrode ispositioned on the same side of the recess as the compliant electrode.Application of a potential difference across the electrodes causes theelectrodes to be attracted such that elastomer material between them iscompressed and bows into the flow channel. Either of theelectrostrictively or the electrostatically-actuated valve structuresmay include an electrically-conducting fluid in the control channel toserve as the compliant electrode.

An embodiment of a method for actuating a valve structure in accordancewith the present invention comprises applying a potential differencebetween a compliant electrode and a second electrode positioned onopposite sides of a first microfabricated recess of an elastomericblock. The compliant electrode is attracted to the second electrode andan associated elastomeric membrane separating the first microfabricatedrecess from a second microfabricated recess is drawn into the firstrecess.

These and other embodiments of the present invention, as well as itsadvantages and features, are described in more detail in conjunctionwith the text below and attached figures.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an illustration of a first elastomeric layer formed on top ofa micromachined mold.

FIG. 2 is an illustration of a second elastomeric layer formed on top ofa micromachined mold.

FIG. 3 is an illustration of the elastomeric layer of FIG. 2 removedfrom the micromachined mold and positioned over the top of theelastomeric layer of FIG. 1

FIG. 4 is an illustration corresponding to FIG. 3, but showing thesecond elastomeric layer positioned on top of the first elastomericlayer.

FIG. 5 is an illustration corresponding to FIG. 4, but showing the firstand second elastomeric layers bonded together.

FIG. 6 is an illustration corresponding to FIG. 5, but showing the firstmicromachined mold removed and a planar substrate positioned in itsplace.

FIG. 7A is an illustration corresponding to FIG. 6, but showing theelastomeric structure sealed onto the planar substrate.

FIG. 7B is a front sectional view corresponding to FIG. 7A, showing anopen flow channel.

FIGS. 7C-7G are illustrations showing steps of a method for forming anelastomeric structure having a membrane formed from a separateelastomeric layer.

FIG. 7H is a front sectional view corresponding to FIG. 7A, showing aclosed flow channel.

FIGS. 8A and 8B illustrate valve opening vs. applied pressure forvarious flow channels.

FIG. 9 illustrates time response of a 100 μm×100 μm×10 μm RTVmicrovalve.

FIG. 10 is an enlarged cross-sectional view of an embodiment of a valvehaving a square flow channel.

FIG. 11 is an enlarged cross-sectional view of an embodiment of a valvehaving an arched flow channel.

FIG. 12A is a top schematic view of an on/off valve.

FIG. 12B is a sectional elevation view along line 23B-23B in FIG. 12AFIG. 13A is a top schematic view of a peristaltic pumping system.

FIG. 13B is a sectional elevation view along line 24B-24B in FIG. 13A

FIG. 14 is a graph showing experimentally achieved pumping rates vs.frequency for an embodiment of the peristaltic pumping system of FIG.13.

FIG. 15A is a top schematic view of one control line actuating multipleflow lines simultaneously.

FIG. 15B is a sectional elevation view along line 26B-26B in FIG. 15A

FIG. 16 is a schematic illustration of a multiplexed system adapted topermit flow through various channels.

FIG. 17A is a plan view of a flow layer of an addressable reactionchamber structure.

FIG. 17B is a bottom plan view of a control channel layer of anaddressable reaction chamber structure.

FIG. 17C is an exploded perspective view of the addressable reactionchamber structure formed by bonding the control channel layer of FIG.17B to the top of the flow layer of FIG. 17A.

FIG. 17D is a sectional elevation view corresponding to FIG. 17C, takenalong line 28D-28D in FIG. 17C.

FIG. 18 is a schematic of a system adapted to selectively direct fluidflow into any of an array of reaction wells.

FIG. 19 is a schematic of a system adapted for selectable lateral flowbetween parallel flow channels.

FIG. 20A is a bottom plan view of first layer (i.e.: the flow channellayer) of elastomer of a switchable flow array.

FIG. 20B is a bottom plan view of a control channel layer of aswitchable flow array.

FIG. 20C shows the alignment of the first layer of elastomer of FIG. 20Awith one set of control channels in the second layer of elastomer ofFIG. 20B.

FIG. 20D also shows the alignment of the first layer of elastomer ofFIG. 20A with the other set of control channels in the second layer ofelastomer of FIG. 20B.

FIGS. 21A-21J show views of one embodiment of a normally-closed valvestructure in accordance with the present invention.

FIGS. 22A and 22B show plan views illustrating operation of oneembodiment of a side-actuated valve structure in accordance with thepresent invention.

FIG. 23 shows a cross-sectional view of one embodiment of a compositestructure in accordance with the present invention.

FIG. 24 shows a cross-sectional view of another embodiment of acomposite structure in accordance with the present invention.

FIG. 25 shows a cross-sectional view of another embodiment of acomposite structure in accordance with the present invention.

FIGS. 26A-26D show plan views illustrating operation of one embodimentof a cell pen structure in accordance with the present invention.

FIGS. 27A-27B show plan and cross-sectional views illustrating operationof one embodiment of a cell cage structure in accordance with thepresent invention.

FIGS. 28A-28B show plan views of operation of a mixing structureutilizing cross-channel injection in accordance with the embodiment ofthe present invention.

FIGS. 29A-29D illustrate cross-sectional views of metering by volumeexclusion in accordance with an embodiment of the present invention.

FIG. 30A shows a simplified cross-sectional view of one embodiment of anelectrostatically actuated valve structure in a nonactuated state. FIG.30B shows a simplified cross-sectional view of the valve structure ofFIG. 30A in an actuated state.

FIG. 31A shows a simplified cross-sectional view of an alternativeembodiment of an electrostatically actuated valve structure in anonactuated state. FIG. 31B shows a simplified cross-sectional view ofthe valve structure of FIG. 31A in an actuated state.

FIG. 32A shows a simplified cross-sectional view of another alternativeembodiment of an electrostatically actuated valve structure in anonactuated state. FIG. 32B shows a simplified cross-sectional view ofthe valve structure of FIG. 32A in an actuated state.

FIG. 33A shows a simplified cross-sectional view of still anotherelectrostatically actuated valve structure in a nonactuated state. FIG.33B shows a simplified cross-sectional view of the valve structure ofFIG. 33A in an actuated state.

FIG. 34A shows a simplified cross-sectional view of one embodiment of anelectrostrictively actuated valve structure in a nonactuated state. FIG.34B shows a simplified cross-sectional view of the valve structure ofFIG. 34A in an actuated state.

FIG. 35A shows a simplified cross-sectional view of another embodimentof an electrostrictively actuated valve structure in a nonactuatedstate. FIG. 35B shows a simplified cross-sectional view of the valvestructure of FIG. 35A in an actuated state.

FIG. 36A shows a simplified cross-sectional view of still anotherembodiment of an electrostrictively actuated valve structure in anonactuated state. FIG. 36B shows a simplified cross-sectional view ofthe valve structure of FIG. 36A in an actuated state.

DETAILED DESCRIPTION OF THE PRESENT INVENTION

I. Microfabrication Overview

The following discussion relates to formation of microfabricated fluidicdevices utilizing elastomer materials, as described generally in U.S.patent application Ser. No. 09/826,585 filed Apr. 6, 2001, Ser. No.09/724,784 filed Nov. 28, 2000, and Ser. No. 09/605,520, filed Jun. 27,2000. These patent applications are hereby incorporated by reference.

1. Methods of Fabricating

Exemplary methods of fabricating the present invention are providedherein. It is to be understood that the present invention is not limitedto fabrication by one or the other of these methods. Rather, othersuitable methods of fabricating the present microstructures, includingmodifying the present methods, are also contemplated.

FIGS. 1 to 7B illustrate sequential steps of a first preferred method offabricating the present microstructure, (which may be used as a pump orvalve). FIGS. 8 to 18 illustrate sequential steps of a second preferredmethod of fabricating the present microstructure which also may be usedas a valve or as pump component.

As will be explained, the preferred method of FIGS. 1 to 7B involvesusing pre-cured elastomer layers which are assembled and bonded. In analternative method, each layer of elastomer may be cured “in place”. Inthe following description “channel” refers to a recess in theelastomeric structure which can contain a flow of fluid or gas.

Referring to FIG. 1, a first micro-machined mold 10 is provided.Micro-machined mold 10 may be fabricated by a number of conventionalsilicon processing methods, including but not limited tophotolithography, ion-milling, and electron beam lithography.

As can be seen, micro-machined mold 10 has a raised line or protrusion11 extending therealong. A first elastomeric layer 20 is cast on top ofmold 10 such that a first recess 21 will be formed in the bottom surfaceof elastomeric layer 20, (recess 21 corresponding in dimension toprotrusion 11), as shown.

As can be seen in FIG. 2, a second micro-machined mold 12 having araised protrusion 13 extending therealong is also provided. A secondelastomeric layer 22 is cast on top of mold 12, as shown, such that arecess 23 will be formed in its bottom surface corresponding to thedimensions of protrusion 13.

As can be seen in the sequential steps illustrated in FIGS. 3 and 4,second elastomeric layer 22 is then removed from mold 12 and placed ontop of first elastomeric layer 20. As can be seen, recess 23 extendingalong the bottom surface of second elastomeric layer 22 will form a flowchannel 32.

Referring to FIG. 5, the separate first and second elastomeric layers 20and 22 (FIG. 4) are then bonded together to form an integrated (i.e.:monolithic) elastomeric structure 24.

As can been seen in the sequential step of FIGS. 6 and 7A, elastomericstructure 24 is then removed from mold 10 and positioned on top of aplanar substrate 14. As can be seen in FIGS. 7A and 7B, when elastomericstructure 24 has been sealed at its bottom surface to planar substrate14, recess 21 will form a flow channel 30.

The present elastomeric structures form a reversible hermetic seal withnearly any smooth planar substrate. An advantage to forming a seal thisway is that the elastomeric structures may be peeled up, washed, andre-used. In preferred aspects, planar substrate 14 is glass. A furtheradvantage of using glass is that glass is transparent, allowing opticalinterrogation of elastomer channels and reservoirs. Alternatively, theelastomeric structure may be bonded onto a flat elastomer layer by thesame method as described above, forming a permanent and high-strengthbond. This may prove advantageous when higher back pressures are used.

As can be seen in FIGS. 7A and 7B, flow channels 30 and 32 arepreferably disposed at an angle to one another with a small membrane 25of substrate 24 separating the top of flow channel 30 from the bottom offlow channel 32.

In preferred aspects, planar substrate 14 is glass. An advantage ofusing glass is that the present elastomeric structures may be peeled up,washed and reused. A further advantage of using glass is that opticalsensing may be employed. Alternatively, planar substrate 14 may be anelastomer itself, which may prove advantageous when higher backpressures are used.

The method of fabrication just described may be varied to form astructure having a membrane composed of an elastomeric materialdifferent than that forming the walls of the channels of the device.This variant fabrication method is illustrated in FIGS. 7C-7G.

Referring to FIG. 7C, a first micro-machined mold 10 is provided.Micro-machined mold 10 has a raised line or protrusion 11 extendingtherealong. In FIG. 7D, first elastomeric layer 20 is cast on top offirst micro-machined mold 10 such that the top of the first elastomericlayer 20 is flush with the top of raised line or protrusion 11. This maybe accomplished by carefully controlling the volume of elastomericmaterial spun onto mold 10 relative to the known height of raised line11. Alternatively, the desired shape could be formed by injectionmolding.

In FIG. 7E, second micro-machined mold 12 having a raised protrusion 13extending therealong is also provided. Second elastomeric layer 22 iscast on top of second mold 12 as shown, such that recess 23 is formed inits bottom surface corresponding to the dimensions of protrusion 13.

In FIG. 7F, second elastomeric layer 22 is removed from mold 12 andplaced on top of third elastomeric layer 222. Second elastomeric layer22 is bonded to third elastomeric layer 20 to form integral elastomericblock 224 using techniques described in detail below. At this point inthe process, recess 23 formerly occupied by raised line 13 will formflow channel 23.

In FIG. 7G, elastomeric block 224 is placed on top of firstmicro-machined mold 10 and first elastomeric layer 20. Elastomeric blockand first elastomeric layer 20 are then bonded together to form anintegrated (i.e.: monolithic) elastomeric structure 24 having a membranecomposed of a separate elastomeric layer 222.

When elastomeric structure 24 has been sealed at its bottom surface to aplanar substrate in the manner described above in connection with FIG.7A, the recess formerly occupied by raised line 11 will form flowchannel 30.

The variant fabrication method illustrated above in conjunction withFIGS. 7C-7G offers the advantage of permitting the membrane portion tobe composed of a separate material than the elastomeric material of theremainder of the structure. This is important because the thickness andelastic properties of the membrane play a key role in operation of thedevice. Moreover, this method allows the separate elastomer layer toreadily be subjected to conditioning prior to incorporation into theelastomer structure. As discussed in detail below, examples ofpotentially desirable condition include the introduction of magnetic orelectrically conducting species to permit actuation of the membrane,and/or the introduction of dopant into the membrane in order to alterits elasticity.

While the above method is illustrated in connection with forming variousshaped elastomeric layers formed by replication molding on top of amicromachined mold, the present invention is not limited to thistechnique. Other techniques could be employed to form the individuallayers of shaped elastomeric material that are to be bonded together.For example, a shaped layer of elastomeric material could be formed bylaser cutting or injection molding, or by methods utilizing chemicaletching and/or sacrificial materials as discussed below in conjunctionwith the second exemplary method.

An alternative method fabricates a patterned elastomer structureutilizing development of photoresist encapsulated within elastomermaterial. However, the methods in accordance with the present inventionare not limited to utilizing photoresist. Other materials such as metalscould also serve as sacrificial materials to be removed selective to thesurrounding elastomer material, and the method would remain within thescope of the present invention. For example, gold metal may be etchedselective to RTV 615 elastomer utilizing the appropriate chemicalmixture.

2. Layer and Channel Dimensions

Microfabricated refers to the size of features of an elastomericstructure fabricated in accordance with an embodiment of the presentinvention. In general, variation in at least one dimension ofmicrofabricated structures is controlled to the micron level, with atleast one dimension being microscopic (i.e. below 1000 μm).Microfabrication typically involves semiconductor or MEMS fabricationtechniques such as photolithography and spincoating that are designedfor to produce feature dimensions on the microscopic level, with atleast some of the dimension of the microfabricated structure requiring amicroscope to reasonably resolve/image the structure.

In preferred aspects, flow channels 30, 32, 60 and 62 preferably havewidth-to-depth ratios of about 10:1. A non-exclusive list of otherranges of width-to-depth ratios in accordance with embodiments of thepresent invention is 0.1:1 to 100:1, more preferably 1:1 to 50:1, morepreferably 2:1 to 20:1, and most preferably 3:1 to 15:1. In an exemplaryaspect, flow channels 30, 32, 60 and 62 have widths of about 1 to 1000microns. A non-exclusive list of other ranges of widths of flow channelsin accordance with embodiments of the present invention is 0.01 to 1000microns, more preferably 0.05 to 1000 microns, more preferably 0.2 to500 microns, more preferably 1 to 250 microns, and most preferably 10 to200 microns. Exemplary channel widths include 0.1 μm, 1 μm, 2 μm, 5 μm,10 μm, 20 μm, 40 μm, 50 μm, 60 μm, 70 μm, 80 μm, 90 μm, 100 μm, 110 μm,120 μm, 130 μm, 140 μm, 150 μm, 160 μm, 170 μm, 180 μm, 190 μm, 200 μm,210 μm, 220 μm, 230 μm, 240 μm, and 250 μm.

Flow channels 30, 32, 60, and 62 have depths of about 1 to 100 microns.A non-exclusive list of other ranges of depths of flow channels inaccordance with embodiments of the present invention is 0.01 to 1000microns, more preferably 0.05 to 500 microns, more preferably 0.2 to 250microns, and more preferably 1 to 100 microns, more preferably 2 to 20microns, and most preferably 5 to 10 microns. Exemplary channel depthsinclude including 0.01 μm, 0.02 μm, 0.05 μm, 0.1 μm, 0.2 μm, 0.5 μm, 1μm, 2 μm, 3 μm, 4 μm, 5 μm, 7.5 μm, 10 μm, 12.5 μm, 15 μm, 17.5 μm, 20μm, 22.5 μm, 25 μm, 30 μm, 40 μm, 50 μm, 75 μm, 100 μm, 150 μm, 200 μm,and 250 μm.

The flow channels are not limited to these specific dimension ranges andexamples given above, and may vary in width in order to affect themagnitude of force required to deflect the membrane as discussed atlength below in conjunction with FIG. 27. For example, extremely narrowflow channels having a width on the order of 0.01 μm may be useful inoptical and other applications, as discussed in detail below.Elastomeric structures which include portions having channels of evengreater width than described above are also contemplated by the presentinvention, and examples of applications of utilizing such wider flowchannels include fluid reservoir and mixing channel structures.

The Elastomeric layers may be cast thick for mechanical stability. In anexemplary embodiment, elastomeric layer 22 of FIG. 1 is 50 microns toseveral centimeters thick, and more preferably approximately 4 mm thick.A non-exclusive list of ranges of thickness of the elastomer layer inaccordance with other embodiments of the present invention is betweenabout 0.1 micron to 10 cm, 1 micron to 5 cm, 10 microns to 2 cm, 100microns to 10 mm.

Accordingly, membrane 25 of FIG. 7B separating flow channels 30 and 32has a typical thickness of between about 0.01 and 1000 microns, morepreferably 0.05 to 500 microns, more preferably 0.2 to 250, morepreferably 1 to 100 microns, more preferably 2 to 50 microns, and mostpreferably 5 to 40 microns. As such, the thickness of elastomeric layer22 is about 100 times the thickness of elastomeric layer 20. Exemplarymembrane thicknesses include 0.01 μm, 0.02 μm, 0.03 μm, 0.05 μm, 0.1 μm,0.2 μm, 0.3 μm, 0.5 μm, 1 μm, 2 μm, 3 μm, 5 μm, 7.5 μm, 10 μm, 12.5 μm,15 μm, 17.5 μm, 20 μm, 22.5 μm, 25 μm, 30 μm, 40 μm, 50 μm, 75 μm, 100μm, 150 μm, 200 μm, 250 μm, 300 μm, 400 μm, 500 μm, 750 μm, and 1000 μm.

3. Soft Lithographic Bonding

Preferably, elastomeric layers are bonded together chemically, usingchemistry that is intrinsic to the polymers comprising the patternedelastomer layers. Most preferably, the bonding comprises two component“addition cure” bonding.

In a preferred aspect, the various layers of elastomer are boundtogether in a heterogenous bonding in which the layers have a differentchemistry. Alternatively, a homogenous bonding may be used in which alllayers would be of the same chemistry. Thirdly, the respective elastomerlayers may optionally be glued together by an adhesive instead. In afourth aspect, the elastomeric layers may be thermoset elastomers bondedtogether by heating.

In one aspect of homogeneous bonding, the elastomeric layers arecomposed of the same elastomer material, with the same chemical entityin one layer reacting with the same chemical entity in the other layerto bond the layers together. In one embodiment, bonding between polymerchains of like elastomer layers may result from activation of acrosslinking agent due to light, heat, or chemical reaction with aseparate chemical species.

Alternatively in a heterogeneous aspect, the elastomeric layers arecomposed of different elastomeric materials, with a first chemicalentity in one layer reacting with a second chemical entity in anotherlayer. In one exemplary heterogenous aspect, the bonding process used tobind respective elastomeric layers together may comprise bondingtogether two layers of RTV 615 silicone. RTV 615 silicone is a two-partaddition-cure silicone rubber. Part A contains vinyl groups andcatalyst; part B contains silicon hydride (Si—H) groups. Theconventional ratio for RTV 615 is 10A:1B. For bonding, one layer may bemade with 30A:1B (i.e. excess vinyl groups) and the other with 3A:1B(i.e. excess Si—H groups). Each layer is cured separately. When the twolayers are brought into contact and heated at elevated temperature, theybond irreversibly forming a monolithic elastomeric substrate.

In an exemplary aspect of the present invention, elastomeric structuresare formed utilizing Sylgard 182, 184 or 186, or aliphatic urethanediacrylates such as (but not limited to) Ebecryl 270 or Irr 245 from UCBChemical.

In one embodiment in accordance with the present invention, two-layerelastomeric structures were fabricated from pure acrylated Urethane Ebe270. A thin bottom layer was spin coated at 8000 rpm for 15 seconds at170° C. The top and bottom layers were initially cured under ultravioletlight for 10 minutes under nitrogen utilizing a Model ELC 500 devicemanufactured by Electrolite corporation. The assembled layers were thencured for an additional 30 minutes. Reaction was catalyzed by a 0.5%vol/vol mixture of Irgacure 500 manufactured by Ciba-Geigy Chemicals.The resulting elastomeric material exhibited moderate elasticity andadhesion to glass.

In another embodiment in accordance with the present invention,two-layer elastomeric structures were fabricated from a combination of25% Ebe 270/50% Irr 245/25% isopropyl alcohol for a thin bottom layer,and pure acrylated Urethane Ebe 270 as a top layer. The thin bottomlayer was initially cured for 5 min, and the top layer initially curedfor 10 minutes, under ultraviolet light under nitrogen utilizing a ModelELC 500 device manufactured by Electrolite corporation. The assembledlayers were then cured for an additional 30 minutes. Reaction wascatalyzed by a 0.5% vol/vol mixture of Irgacure 500 manufactured byCiba-Geigy Chemicals. The resulting elastomeric material exhibitedmoderate elasticity and adhered to glass.

Alternatively, other bonding methods may be used, including activatingthe elastomer surface, for example by plasma exposure, so that theelastomer layers/substrate will bond when placed in contact. Forexample, one possible approach to bonding together elastomer layerscomposed of the same material is set forth by Duffy et al, “RapidPrototyping of Microfluidic Systems in Poly (dimethylsiloxane)”,Analytical Chemistry (1998), 70, 4974-4984, incorporated herein byreference. This paper discusses that exposing polydimethylsiloxane(PDMS) layers to oxygen plasma causes oxidation of the surface, withirreversible bonding occurring when the two oxidized layers are placedinto contact.

Yet another approach to bonding together successive layers of elastomeris to utilize the adhesive properties of uncured elastomer.Specifically, a thin layer of uncured elastomer such as RTV 615 isapplied on top of a first cured elastomeric layer. Next, a second curedelastomeric layer is placed on top of the uncured elastomeric layer. Thethin middle layer of uncured elastomer is then cured to produce amonolithic elastomeric structure. Alternatively, uncured elastomer canbe applied to the bottom of a first cured elastomer layer, with thefirst cured elastomer layer placed on top of a second cured elastomerlayer. Curing the middle thin elastomer layer again results in formationof a monolithic elastomeric structure.

Where encapsulation of sacrificial layers is employed to fabricate theelastomer structure, bonding of successive elastomeric layers may beaccomplished by pouring uncured elastomer over a previously curedelastomeric layer and any sacrificial material patterned thereupon.Bonding between elastomer layers occurs due to interpenetration andreaction of the polymer chains of an uncured elastomer layer with thepolymer chains of a cured elastomer layer. Subsequent curing of theelastomeric layer will create a bond between the elastomeric layers andcreate a monolithic elastomeric structure.

Referring to the first method of FIGS. 1 to 7B, first elastomeric layer20 may be created by spin-coating an RTV mixture on microfabricated mold12 at 2000 rpm's for 30 seconds yielding a thickness of approximately 40microns. Second elastomeric layer 22 may be created by spin-coating anRTV mixture on microfabricated mold 11. Both layers 20 and 22 may beseparately baked or cured at about 80° C. for 1.5 hours. The secondelastomeric layer 22 may be bonded onto first elastomeric layer 20 atabout 80° C. for about 1.5 hours.

Micromachined molds 10 and 12 may be patterned photoresist on siliconwafers. In an exemplary aspect, a Shipley SJR 5740 photoresist was spunat 2000 rpm patterned with a high resolution transparency film as a maskand then developed yielding an inverse channel of approximately 10microns in height. When baked at approximately 200° C. for about 30minutes, the photoresist reflows and the inverse channels becomerounded. In preferred aspects, the molds may be treated withtrimethylchlorosilane (TMCS) vapor for about a minute before each use inorder to prevent adhesion of silicone rubber.

4. Suitable Elastomeric Materials

Allcock et al, Contemporary Polymer Chemistry, 2^(nd) Ed. describeselastomers in general as polymers existing at a temperature betweentheir glass transition temperature and liquefaction temperature.Elastomeric materials exhibit elastic properties because the polymerchains readily undergo torsional motion to permit uncoiling of thebackbone chains in response to a force, with the backbone chainsrecoiling to assume the prior shape in the absence of the force. Ingeneral, elastomers deform when force is applied, but then return totheir original shape when the force is removed. The elasticity exhibitedby elastomeric materials may be characterized by a Young's modulus.Elastomeric materials having a Young's modulus of between about 1 Pa-1TPa, more preferably between about 10 Pa-100 GPa, more preferablybetween about 20 Pa-1 GPa, more preferably between about 50 Pa-10 MPa,and more preferably between about 100 Pa-1 MPa are useful in accordancewith the present invention, although elastomeric materials having aYoung's modulus outside of these ranges could also be utilized dependingupon the needs of a particular application.

The systems of the present invention may be fabricated from a widevariety of elastomers. In an exemplary aspect, the elastomeric layersmay preferably be fabricated from silicone rubber. However, othersuitable elastomers may also be used.

In an exemplary aspect of the present invention, the present systems arefabricated from an elastomeric polymer such as GE RTV 615 (formulation),a vinyl-silane crosslinked (type) silicone elastomer (family). However,the present systems are not limited to this one formulation, type oreven this family of polymer; rather, nearly any elastomeric polymer issuitable. An important requirement for the preferred method offabrication of the present microvalves is the ability to bond multiplelayers of elastomers together. In the case of multilayer softlithography, layers of elastomer are cured separately and then bondedtogether. This scheme requires that cured layers possess sufficientreactivity to bond together. Either the layers may be of the same type,and are capable of bonding to themselves, or they may be of twodifferent types, and are capable of bonding to each other. Otherpossibilities include the use an adhesive between layers and the use ofthermoset elastomers.

Given the tremendous diversity of polymer chemistries, precursors,synthetic methods, reaction conditions, and potential additives, thereare a huge number of possible elastomer systems that could be used tomake monolithic elastomeric microvalves and pumps. Variations in thematerials used will most likely be driven by the need for particularmaterial properties, i.e. solvent resistance, stiffness, gaspermeability, or temperature stability.

There are many, many types of elastomeric polymers. A brief descriptionof the most common classes of elastomers is presented here, with theintent of showing that even with relatively “standard” polymers, manypossibilities for bonding exist. Common elastomeric polymers includepolyisoprene, polybutadiene, polychloroprene, polyisobutylene,poly(styrene-butadiene-styrene), the polyurethanes, and silicones.

Polyisoprene, polybutadiene, polychloroprene:

-   -   Polyisoprene, polybutadiene, and polychloroprene are all        polymerized from diene monomers, and therefore have one double        bond per monomer when polymerized. This double bond allows the        polymers to be converted to elastomers by vulcanization        (essentially, sulfur is used to form crosslinks between the        double bonds by heating). This would easily allow homogeneous        multilayer soft lithography by incomplete vulcanization of the        layers to be bonded; photoresist encapsulation would be possible        by a similar mechanism.        Polyisobutylene:    -   Pure polyisobutylene has no double bonds, but is crosslinked to        use as an elastomer by including a small amount (˜1%) of        isoprene in the polymerization. The isoprene monomers give        pendant double bonds on the polyisobutylene backbone, which may        then be vulcanized as above.        (styrene-butadiene-styrene):    -   Poly(styrene-butadiene-styrene) is produced by living anionic        polymerization (that is, there is no natural chain-terminating        step in the reaction), so “live” polymer ends can exist in the        cured polymer. This makes it a natural candidate for the present        photoresist encapsulation system (where there will be plenty of        unreacted monomer in the liquid layer poured on top of the cured        layer). Incomplete curing would allow homogeneous multilayer        soft lithography (A to A bonding). The chemistry also        facilitates making one layer with extra butadiene (“A”) and        coupling agent and the other layer (“B”) with a butadiene        deficit (for heterogeneous multilayer soft lithography). SBS is        a “thermoset elastomer”, meaning that above a certain        temperature it melts and becomes plastic (as opposed to        elastic); reducing the temperature yields the elastomer again.        Thus, layers can be bonded together by heating.        Polyurethanes:    -   Polyurethanes are produced from di-isocyanates (A-A) and        di-alcohols or di-amines (B-B); since there are a large variety        of di-isocyanates and di-alcohols/amines, the number of        different types of polyurethanes is huge. The A vs. B nature of        the polymers, however, would make them useful for heterogeneous        multilayer soft lithography just as RTV 615 is: by using excess        A-A in one layer and excess B-B in the other layer.        Silicones:    -   Silicone polymers probably have the greatest structural variety,        and almost certainly have the greatest number of commercially        available formulations. The vinyl-to-(Si—H) crosslinking of RTV        615 (which allows both heterogeneous multilayer soft lithography        and photoresist encapsulation) has already been discussed, but        this is only one of several crosslinking methods used in        silicone polymer chemistry.

5. Operation of Device

FIGS. 7B and 7H together show the closing of a first flow channel bypressurizing a second flow channel, with FIG. 7B (a front sectional viewcutting through flow channel 32 in corresponding FIG. 7A), showing anopen first flow channel 30; with FIG. 7H showing first flow channel 30closed by pressurization of the second flow channel 32.

Referring to FIG. 7B, first flow channel 30 and second flow channel 32are shown. Membrane 25 separates the flow channels, forming the top offirst flow channel 30 and the bottom of second flow channel 32. As canbe seen, flow channel 30 is “open”.

As can be seen in FIG. 7H, pressurization of flow channel 32 (either bygas or liquid introduced therein) causes membrane 25 to deflectdownward, thereby pinching off flow F passing through flow channel 30.Accordingly, by varying the pressure in channel 32, a linearly actuablevalving system is provided such that flow channel 30 can be opened orclosed by moving membrane 25 as desired. (For illustration purposesonly, channel 30 in FIG. 7G is shown in a “mostly closed” position,rather than a “fully closed” position).

Since such valves are actuated by moving the roof of the channelsthemselves (i.e.: moving membrane 25) valves and pumps produced by thistechnique have a truly zero dead volume, and switching valves made bythis technique have a dead volume approximately equal to the activevolume of the valve, for example about 100×100×10 μm=100 pL. Such deadvolumes and areas consumed by the moving membrane are approximately twoorders of magnitude smaller than known conventional microvalves. Smallerand larger valves and switching valves are contemplated in the presentinvention, and a non-exclusive list of ranges of dead volume includes 1aL to 1 uL, 100 aL to 100 nL, 1 fL to 10 nL, 100 fL to 1 nL, and 1 pL to100 pL

The extremely small volumes capable of being delivered by pumps andvalves in accordance with the present invention represent a substantialadvantage. Specifically, the smallest known volumes of fluid capable ofbeing manually metered is around 0.1 μl. The smallest known volumescapable of being metered by automated systems is about ten-times larger(1 μl). Utilizing pumps and valves in accordance with the presentinvention, volumes of liquid of 10 nl or smaller can routinely bemetered and dispensed. The accurate metering of extremely small volumesof fluid enabled by the present invention would be extremely valuable ina large number of biological applications, including diagnostic testsand assays.

Equation 1 represents a highly simplified mathematical model ofdeflection of a rectangular, linear, elastic, isotropic plate of uniformthickness by an applied pressure:w=(BPb ⁴)/(Eh ³), where:  (1)

-   -   w=deflection of plate;    -   B=shape coefficient (dependent upon length vs. width and support        of edges of plate);    -   P=applied pressure;    -   b=plate width    -   E=Young's modulus; and    -   h=plate thickness.        Thus even in this extremely simplified expression, deflection of        an elastomeric membrane in response to a pressure will be a        function of: the length, width, and thickness of the membrane,        the flexibility of the membrane (Young's modulus), and the        applied actuation force. Because each of these parameters will        vary widely depending upon the actual dimensions and physical        composition of a particular elastomeric device in accordance        with the present invention, a wide range of membrane thicknesses        and elasticities, channel widths, and actuation forces are        contemplated by the present invention.

It should be understood that the formula just presented is only anapproximation, since in general the membrane does not have uniformthickness, the membrane thickness is not necessarily small compared tothe length and width, and the deflection is not necessarily smallcompared to length, width, or thickness of the membrane. Nevertheless,the equation serves as a useful guide for adjusting variable parametersto achieve a desired response of deflection versus applied force.

FIGS. 8A and 8B illustrate valve opening vs. applied pressure for a 100μm wide first flow channel 30 and a 50 μm wide second flow channel 32.The membrane of this device was formed by a layer of General ElectricSilicones RTV 615 having a thickness of approximately 30 μm and aYoung's modulus of approximately 750 kPa. FIGS. 21 a and 21 b show theextent of opening of the valve to be substantially linear over most ofthe range of applied pressures.

Air pressure was applied to actuate the membrane of the device through a10 cm long piece of plastic tubing having an outer diameter of 0.025″connected to a 25 mm piece of stainless steel hypodermic tubing with anouter diameter of 0.025″ and an inner diameter of 0.013″. This tubingwas placed into contact with the control channel by insertion into theelastomeric block in a direction normal to the control channel. Airpressure was applied to the hypodermic tubing from an external LHDAminiature solenoid valve manufactured by Lee Co.

While control of the flow of material through the device has so far beendescribed utilizing applied gas pressure, other fluids could be used.

For example, air is compressible, and thus experiences some finite delaybetween the time of application of pressure by the external solenoidvalve and the time that this pressure is experienced by the membrane. Inan alternative embodiment of the present invention, pressure could beapplied from an external source to a noncompressible fluid such as wateror hydraulic oils, resulting in a near-instantaneous transfer of appliedpressure to the membrane. However, if the displaced volume of the valveis large or the control channel is narrow, higher viscosity of a controlfluid may contribute to delay in actuation. The optimal medium fortransferring pressure will therefore depend upon the particularapplication and device configuration, and both gaseous and liquid mediaare contemplated by the invention.

While external applied pressure as described above has been applied by apump/tank system through a pressure regulator and external miniaturevalve, other methods of applying external pressure are also contemplatedin the present invention, including gas tanks, compressors, pistonsystems, and columns of liquid. Also contemplated is the use ofnaturally occurring pressure sources such as may be found inside livingorganisms, such as blood pressure, gastric pressure, the pressurepresent in the cerebro-spinal fluid, pressure present in theintra-ocular space, and the pressure exerted by muscles during normalflexure. Other methods of regulating external pressure are alsocontemplated, such as miniature valves, pumps, macroscopic peristalticpumps, pinch valves, and other types of fluid regulating equipment suchas is known in the art.

As can be seen, the response of valves in accordance with embodiments ofthe present invention have been experimentally shown to be almostperfectly linear over a large portion of its range of travel, withminimal hysteresis. Accordingly, the present valves are ideally suitedfor microfluidic metering and fluid control. The linearity of the valveresponse demonstrates that the individual valves are well modeled asHooke's Law springs. Furthermore, high pressures in the flow channel(i.e.: back pressure) can be countered simply by increasing theactuation pressure. Experimentally, the present inventors have achievedvalve closure at back pressures of 70 kPa, but higher pressures are alsocontemplated. The following is a nonexclusive list of pressure rangesencompassed by the present invention: 10 Pa-25 MPa; 100 Pa-10 Mpa, 1kPa-1 MPa, 1 kPa-300 kPa, 5 kPa-200 kPa, and 15 kPa-100 kPa.

While valves and pumps do not require linear actuation to open andclose, linear response does allow valves to more easily be used asmetering devices. In one embodiment of the invention, the opening of thevalve is used to control flow rate by being partially actuated to aknown degree of closure. Linear valve actuation makes it easier todetermine the amount of actuation force required to close the valve to adesired degree of closure. Another benefit of linear actuation is thatthe force required for valve actuation may be easily determined from thepressure in the flow channel. If actuation is linear, increased pressurein the flow channel may be countered by adding the same pressure (forceper unit area) to the actuated portion of the valve.

Linearity of a valve depends on the structure, composition, and methodof actuation of the valve structure. Furthermore, whether linearity is adesirable characteristic in a valve depends on the application.Therefore, both linearly and non-linearly actuable valves arecontemplated in the present invention, and the pressure ranges overwhich a valve is linearly actuable will vary with the specificembodiment.

FIG. 9 illustrates time response (i.e.: closure of valve as a functionof time in response to a change in applied pressure) of a 100 μm×100μm×10 μm RTV microvalve with 10-cm-long air tubing connected from thechip to a pneumatic valve as described above.

Two periods of digital control signal, actual air pressure at the end ofthe tubing and valve opening are shown in FIG. 9. The pressure appliedon the control line is 100 kPa, which is substantially higher than the˜40 kPa required to close the valve. Thus, when closing, the valve ispushed closed with a pressure 60 kPa greater than required. Whenopening, however, the valve is driven back to its rest position only byits own spring force (≦40 kPa). Thus, τ_(close) is expected to besmaller than τ_(open). There is also a lag between the control signaland control pressure response, due to the limitations of the miniaturevalve used to control the pressure. Calling such lags t and the 1/e timeconstants τ, the values are: t_(open)=3.63 ms, τ_(open)=1.88 ms,t_(close)=2.15 ms, τ_(close)=0.51 ms. If 3τ each are allowed for openingand closing, the valve runs comfortably at 75 Hz when filled withaqueous solution.

If one used another actuation method which did not suffer from openingand closing lag, this valve would run at ˜375 Hz. Note also that thespring constant can be adjusted by changing the membrane thickness; thisallows optimization for either fast opening or fast closing. The springconstant could also be adjusted by changing the elasticity (Young'smodulus) of the membrane, as is possible by introducing dopant into themembrane or by utilizing a different elastomeric material to serve asthe membrane (described above in conjunction with FIGS. 7C-7H.)

When experimentally measuring the valve properties as illustrated inFIG. 9 the valve opening was measured by fluorescence. In theseexperiments, the flow channel was filled with a solution of fluoresceinisothiocyanate (FITC) in buffer (pH≧8) and the fluorescence of a squarearea occupying the center ˜⅓rd of the channel is monitored on anepi-fluorescence microscope with a photomultiplier tube with a 10 kHzbandwidth. The pressure was monitored with a Wheatstone-bridge pressuresensor (SenSym SCC15GD2) pressurized simultaneously with the controlline through nearly identical pneumatic connections.

6. Flow Channel Cross Sections

The flow channels of the present invention may optionally be designedwith different cross sectional sizes and shapes, offering differentadvantages, depending upon their desired application. For example, thecross sectional shape of the lower flow channel may have a curved uppersurface, either along its entire length or in the region disposed underan upper cross channel). Such a curved upper surface facilitates valvesealing, as follows.

Referring to FIG. 10, a cross sectional view (similar to that of FIG.7B) through flow channels 30 and 32 is shown. As can be seen, flowchannel 30 is rectangular in cross sectional shape. In an alternatepreferred aspect of the invention, as shown in FIG. 20, thecross-section of a flow channel 30 instead has an upper curved surface.

Referring first to FIG. 10, when flow channel 32 is pressurized, themembrane portion 25 of elastomeric block 24 separating flow channels 30and 32 will move downwardly to the successive positions shown by thedotted lines 25A, 25B, 25C, 25D, and 25E. As can be seen, incompletesealing may possibly result at the edges of flow channel 30 adjacentplanar substrate 14.

In the alternate preferred embodiment of FIG. 11, flow channel 30 a hasa curved upper wall 25A. When flow channel 32 is pressurized, membraneportion 25 will move downwardly to the successive positions shown bydotted lines 25A2, 25A3, 25A4 and 25A5, with edge portions of themembrane moving first into the flow channel, followed by top membraneportions. An advantage of having such a curved upper surface at membrane25A is that a more complete seal will be provided when flow channel 32is pressurized. Specifically, the upper wall of the flow channel 30 willprovide a continuous contacting edge against planar substrate 14,thereby avoiding the “island” of contact seen between wall 25 and thebottom of flow channel 30 in FIG. 10.

Another advantage of having a curved upper flow channel surface atmembrane 25A is that the membrane can more readily conform to the shapeand volume of the flow channel in response to actuation. Specifically,where a rectangular flow channel is employed, the entire perimeter (2×flow channel height, plus the flow channel width) must be forced intothe flow channel. However where an arched flow channel is used, asmaller perimeter of material (only the semi-circular arched portion)must be forced into the channel. In this manner, the membrane requiresless change in perimeter for actuation and is therefore more responsiveto an applied actuation force to block the flow channel

In an alternate aspect, (not illustrated), the bottom of flow channel 30is rounded such that its curved surface mates with the curved upper wall25A as seen in FIG. 20 described above.

In summary, the actual conformational change experienced by the membraneupon actuation will depend upon the configuration of the particularelastomeric structure. Specifically, the conformational change willdepend upon the length, width, and thickness profile of the membrane,its attachment to the remainder of the structure, and the height, width,and shape of the flow and control channels and the material propertiesof the elastomer used. The conformational change may also depend uponthe method of actuation, as actuation of the membrane in response to anapplied pressure will vary somewhat from actuation in response to amagnetic or electrostatic force.

Moreover, the desired conformational change in the membrane will alsovary depending upon the particular application for the elastomericstructure. In the simplest embodiments described above, the valve mayeither be open or closed, with metering to control the degree of closureof the valve. In other embodiments however, it may be desirable to alterthe shape of the membrane and/or the flow channel in order to achievemore complex flow regulation. For instance, the flow channel could beprovided with raised protrusions beneath the membrane portion, such thatupon actuation the membrane shuts off only a percentage of the flowthrough the flow channel, with the percentage of flow blockedinsensitive to the applied actuation force.

Many membrane thickness profiles and flow channel cross-sections arecontemplated by the present invention, including rectangular,trapezoidal, circular, ellipsoidal, parabolic, hyperbolic, andpolygonal, as well as sections of the above shapes. More complexcross-sectional shapes, such as the embodiment with protrusionsdiscussed immediately above or an embodiment having concavities in theflow channel, are also contemplated by the present invention.

In addition, while the invention is described primarily above inconjunction with an embodiment wherein the walls and ceiling of the flowchannel are formed from elastomer, and the floor of the channel isformed from an underlying substrate, the present invention is notlimited to this particular orientation. Walls and floors of channelscould also be formed in the underlying substrate, with only the ceilingof the flow channel constructed from elastomer. This elastomer flowchannel ceiling would project downward into the channel in response toan applied actuation force, thereby controlling the flow of materialthrough the flow channel. In general, monolithic elastomer structures asdescribed elsewhere in the instant application are preferred formicrofluidic applications. However, it may be useful to employ channelsformed in the substrate where such an arrangement provides advantages.For instance, a substrate including optical waveguides could beconstructed so that the optical waveguides direct light specifically tothe side of a microfluidic channel.

7. Alternate Valve Actuation Techniques

In addition to pressure based actuation systems described above,optional electrostatic and magnetic actuation systems are alsocontemplated, as follows.

Electrostatic actuation can be accomplished by forming oppositelycharged electrodes (which will tend to attract one another when avoltage differential is applied to them) directly into the monolithicelastomeric structure. For example, referring to FIG. 7B, an optionalfirst electrode 70 (shown in phantom) can be positioned on (or in)membrane 25 and an optional second electrode 72 (also shown in phantom)can be positioned on (or in) planar substrate 14. When electrodes 70 and72 are charged with opposite polarities, an attractive force between thetwo electrodes will cause membrane 25 to deflect downwardly, therebyclosing the “valve” (i.e.: closing flow channel 30).

For the membrane electrode to be sufficiently conductive to supportelectrostatic actuation, but not so mechanically stiff so as to impedethe valve's motion, a sufficiently flexible electrode must be providedin or over membrane 25. Such an electrode may be provided by a thinmetallization layer, doping the polymer with conductive material, ormaking the surface layer out of a conductive material.

In an exemplary aspect, the electrode present at the deflecting membranecan be provided by a thin metallization layer which can be provided, forexample, by sputtering a thin layer of metal such as 20 nm of gold. Inaddition to the formation of a metallized membrane by sputtering, othermetallization approaches such as chemical epitaxy, evaporation,electroplating, and electroless plating are also available. Physicaltransfer of a metal layer to the surface of the elastomer is alsoavailable, for example by evaporating a metal onto a flat substrate towhich it adheres poorly, and then placing the elastomer onto the metaland peeling the metal off of the substrate.

A conductive electrode 70 may also be formed by depositing carbon black(i.e. Cabot Vulcan XC72R) on the elastomer surface, either by wiping onthe dry powder or by exposing the elastomer to a suspension of carbonblack in a solvent which causes swelling of the elastomer, (such as achlorinated solvent in the case of PDMS). Alternatively, the electrode70 may be formed by constructing the entire layer 20 out of elastomerdoped with conductive material (i.e. carbon black or finely dividedmetal particles). Yet further alternatively, the electrode may be formedby electrostatic deposition, or by a chemical reaction that producescarbon. In experiments conducted by the present inventors, conductivitywas shown to increase with carbon black concentration from 5.6×10⁻¹⁶ toabout 5×10⁻³ (Q-cm)⁻¹. The lower electrode 72, which is not required tomove, may be either a compliant electrode as described above, or aconventional electrode such as evaporated gold, a metal plate, or adoped semiconductor electrode.

Magnetic actuation of the flow channels can be achieved by fabricatingthe membrane separating the flow channels with a magneticallypolarizable material such as iron, or a permanently magnetized materialsuch as polarized NdFeB. In experiments conducted by the presentinventors, magnetic silicone was created by the addition of iron powder(about 1 um particle size), up to 20% iron by weight.

Where the membrane is fabricated with a magnetically polarizablematerial, the membrane can be actuated by attraction in response to anapplied magnetic field Where the membrane is fabricated with a materialcapable of maintaining permanent magnetization, the material can firstbe magnetized by exposure to a sufficiently high magnetic field, andthen actuated either by attraction or repulsion in response to thepolarity of an applied inhomogenous magnetic field.

The magnetic field causing actuation of the membrane can be generated ina variety of ways. In one embodiment, the magnetic field is generated byan extremely small inductive coil formed in or proximate to theelastomer membrane. The actuation effect of such a magnetic coil wouldbe localized, allowing actuation of individual pump and/or valvestructures. Alternatively, the magnetic field could be generated by alarger, more powerful source, in which case actuation would be globaland would actuate multiple pump and/or valve structures at one time.

It is also possible to actuate the device by causing a fluid flow in thecontrol channel based upon the application of thermal energy, either bythermal expansion or by production of gas from liquid. For example, inone alternative embodiment in accordance with the present invention, apocket of fluid (e.g. in a fluid-filled control channel) is positionedover the flow channel. Fluid in the pocket can be in communication witha temperature variation system, for example a heater. Thermal expansionof the fluid, or conversion of material from the liquid to the gasphase, could result in an increase in pressure, closing the adjacentflow channel. Subsequent cooling of the fluid would relieve pressure andpermit the flow channel to open.

8. Networked Systems

FIGS. 12A and 12B show a views of a single on/off valve, identical tothe systems set forth above, (for example in FIG. 7A). FIGS. 13A and 13Bshows a peristaltic pumping system comprised of a plurality of thesingle addressable on/off valves as seen in FIG. 12, but networkedtogether. FIG. 14 is a graph showing experimentally achieved pumpingrates vs. frequency for the peristaltic pumping system of FIG. 13. FIGS.15A and 15B show a schematic view of a plurality of flow channels whichare controllable by a single control line. This system is also comprisedof a plurality of the single addressable on/off valves of FIG. 12,multiplexed together, but in a different arrangement than that of FIG.12. FIG. 16 is a schematic illustration of a multiplexing system adaptedto permit fluid flow through selected channels, comprised of a pluralityof the single on/off valves of FIG. 12, joined or networked together.

Referring first to FIGS. 12A and 12B, a schematic of flow channels 30and 32 is shown. Flow channel 30 preferably has a fluid (or gas) flow Fpassing therethrough. Flow channel 32, (which crosses over flow channel30, as was already explained herein), is pressurized such that membrane25 separating the flow channels may be depressed into the path of flowchannel 30, shutting off the passage of flow F therethrough, as has beenexplained. As such, “flow channel” 32 can also be referred to as a“control line” which actuates a single valve in flow channel 30. InFIGS. 12 to 15, a plurality of such addressable valves are joined ornetworked together in various arrangements to produce pumps, capable ofperistaltic pumping, and other fluidic logic applications.

Referring to FIGS. 13A and 13B, a system for peristaltic pumping isprovided, as follows. A flow channel 30 has a plurality of generallyparallel flow channels (i.e.: control lines) 32A, 32B and 32C passingthereover. By pressurizing control line 32A, flow F through flow channel30 is shut off under membrane 25A at the intersection of control line32A and flow channel 30. Similarly, (but not shown), by pressurizingcontrol line 32B, flow F through flow channel 30 is shut off undermembrane 25B at the intersection of control line 32B and flow channel30, etc.

Each of control lines 32A, 32B, and 32C is separately addressable.Therefore, peristalsis may be actuated by the pattern of actuating 32Aand 32C together, followed by 32A, followed by 32A and 32B together,followed by 32B, followed by 32B and C together, etc. This correspondsto a successive “101, 100, 110, 010, 011, 001” pattern, where “0”indicates “valve open” and “1” indicates “valve closed.” Thisperistaltic pattern is also known as a 120° pattern (referring to thephase angle of actuation between three valves). Other peristalticpatterns are equally possible, including 60° and 90° patterns.

In experiments performed by the inventors, a pumping rate of 2.35 nL/swas measured by measuring the distance traveled by a column of water inthin (0.5 mm i.d.) tubing; with 100×100×10 μm valves under an actuationpressure of 40 kPa. The pumping rate increased with actuation frequencyuntil approximately 75 Hz, and then was nearly constant until above 200Hz. The valves and pumps are also quite durable and the elastomermembrane, control channels, or bond have never been observed to fail. Inexperiments performed by the inventors, none of the valves in theperistaltic pump described herein show any sign of wear or fatigue aftermore than 4 million actuations. In addition to their durability, theyare also gentle. A solution of E. Coli pumped through a channel andtested for viability showed a 94% survival rate.

FIG. 14 is a graph showing experimentally achieved pumping rates vs.frequency for the peristaltic pumping system of FIG. 13.

FIGS. 15A and 15B illustrates another way of assembling a plurality ofthe addressable valves of FIG. 12. Specifically, a plurality of parallelflow channels 30A, 30B, and 30C are provided. Flow channel (i.e.:control line) 32 passes thereover across flow channels 30A, 30B, and30C. Pressurization of control line 32 simultaneously shuts off flowsF1, F2 and F3 by depressing membranes 25A, 25B, and 25C located at theintersections of control line 32 and flow channels 30A, 30B, and 30C.

FIG. 16 is a schematic illustration of a multiplexing system adapted toselectively permit fluid to flow through selected channels, as follows.The downward deflection of membranes separating the respective flowchannels from a control line passing thereabove (for example, membranes25A, 25B, and 25C in FIGS. 15A and 15B) depends strongly upon themembrane dimensions. Accordingly, by varying the widths of flow channelcontrol line 32 in FIGS. 15A and 15B, it is possible to have a controlline pass over multiple flow channels, yet only actuate (i.e.: seal)desired flow channels. FIG. 16 illustrates a schematic of such a system,as follows.

A plurality of parallel flow channels 30A, 30B, 30C, 30D, 30E and 30Fare positioned under a plurality of parallel control lines 32A, 32B,32C, 32D, 32E and 32F. Control channels 32A, 32B, 32C, 32D, 32E and 32Fare adapted to shut off fluid flows F1, F2, F3, F4, F5 and F6 passingthrough parallel flow channels 30A, 30B, 30C, 30D, 30E and 30F using anyof the valving systems described above, with the following modification.

Each of control lines 32A, 32B, 32C, 32D, 32E and 32F have both wide andnarrow portions. For example, control line 32A is wide in locationsdisposed over flow channels 30A, 30C and 30E. Similarly, control line32B is wide in locations disposed over flow channels 30B, 30D and 30F,and control line 32C is wide in locations disposed over flow channels30A, 30B, 30E and 30F.

At the locations where the respective control line is wide, itspressurization will cause the membrane (25) separating the flow channeland the control line to depress significantly into the flow channel,thereby blocking the flow passage therethrough. Conversely, in thelocations where the respective control line is narrow, membrane (25)will also be narrow. Accordingly, the same degree of pressurization willnot result in membrane (25) becoming depressed into the flow channel(30). Therefore, fluid passage thereunder will not be blocked.

For example, when control line 32A is pressurized, it will block flowsF1, F3 and F5 in flow channels 30A, 30C and 30E. Similarly, when controlline 32C is pressurized, it will block flows F1, F2, F5 and F6 in flowchannels 30A, 30B, 30E and 30F. As can be appreciated, more than onecontrol line can be actuated at the same time. For example, controllines 32A and 32C can be pressurized simultaneously to block all fluidflow except F4 (with 32A blocking F1, F3 and F5; and 32C blocking F1,F2, F5 and F6).

By selectively pressurizing different control lines (32) both togetherand in various sequences, a great degree of fluid flow control can beachieved. Moreover, by extending the present system to more than sixparallel flow channels (30) and more than four parallel control lines(32), and by varying the positioning of the wide and narrow regions ofthe control lines, very complex fluid flow control systems may befabricated. A property of such systems is that it is possible to turn onany one flow channel out of n flow channels with only 2(log₂n) controllines.

9. Selectively Addressable Reaction Chambers Along Flow Lines

In a further embodiment of the invention, illustrated in FIGS. 17A, 17B,17C and 17D, a system for selectively directing fluid flow into one moreof a plurality of reaction chambers disposed along a flow line isprovided.

FIG. 17A shows a top view of a flow channel 30 having a plurality ofreaction chambers 80A and 80B disposed therealong. Preferably flowchannel 30 and reaction chambers 80A and 80B are formed together asrecesses into the bottom surface of a first layer 100 of elastomer.

FIG. 17B shows a bottom plan view of another elastomeric layer 110 withtwo control lines 32A and 32B each being generally narrow, but havingwide extending portions 33A and 33B formed as recesses therein.

As seen in the exploded view of FIG. 17C, and assembled view of FIG.17D, elastomeric layer 110 is placed over elastomeric layer 100. Layers100 and 110 are then bonded together, and the integrated system operatesto selectively direct fluid flow F (through flow channel 30) into eitheror both of reaction chambers 80A and 80B, as follows. Pressurization ofcontrol line 32A will cause the membrane 25 (i.e.: the thin portion ofelastomer layer 100 located below extending portion 33A and over regions82A of reaction chamber 80A) to become depressed, thereby shutting offfluid flow passage in regions 82A, effectively sealing reaction chamber80 from flow channel 30. As can also be seen, extending portion 33A iswider than the remainder of control line 32A. As such, pressurization ofcontrol line 32A will not result in control line 32A sealing flowchannel 30.

As can be appreciated, either or both of control lines 32A and 32B canbe actuated at once. When both control lines 32A and 32B are pressurizedtogether, sample flow in flow channel 30 will enter neither of reactionchambers 80A or 80B.

The concept of selectably controlling fluid introduction into variousaddressable reaction chambers disposed along a flow line (FIGS. 17A-D)can be combined with concept of selectably controlling fluid flowthrough one or more of a plurality of parallel flow lines (FIG. 16) toyield a system in which a fluid sample or samples can be can be sent toany particular reaction chamber in an array of reaction chambers. Anexample of such a system is provided in FIG. 18, in which parallelcontrol channels 32A, 32B and 32C with extending portions 34 (all shownin phantom) selectively direct fluid flows F1 and F2 into any of thearray of reaction wells 80A, 80B, 80C or 80D as explained above; whilepressurization of control lines 32C and 32D selectively shuts off flowsF2 and F1, respectively.

In yet another novel embodiment, fluid passage between parallel flowchannels is possible. Referring to FIG. 19, either or both of controllines 32A or 32D can be depressurized such that fluid flow throughlateral passageways 35 (between parallel flow channels 30A and 30B) ispermitted. In this aspect of the invention, pressurization of controllines 32C and 32D would shut flow channel 30A between 35A and 35B, andwould also shut lateral passageways 35B. As such, flow entering as flowF1 would sequentially travel through 30A, 35A and leave 30B as flow F4.

10. Switchable Flow Arrays

In yet another novel embodiment, fluid passage can be selectivelydirected to flow in either of two perpendicular directions. An exampleof such a “switchable flow array” system is provided in FIGS. 20A to20D. FIG. 20A shows a bottom view of a first layer of elastomer 90, (orany other suitable substrate), having a bottom surface with a pattern ofrecesses forming a flow channel grid defined by an array of solid posts92, each having flow channels passing therearound.

In preferred aspects, an additional layer of elastomer is bound to thetop surface of layer 90 such that fluid flow can be selectively directedto move either in direction F1, or perpendicular direction F2. FIG. 20is a bottom view of the bottom surface of the second layer of elastomer95 showing recesses formed in the shape of alternating “vertical”control lines 96 and “horizontal” control lines 94. “Vertical” controllines 96 have the same width therealong, whereas “horizontal” controllines 94 have alternating wide and narrow portions, as shown.

Elastomeric layer 95 is positioned over top of elastomeric layer 90 suchthat “vertical” control lines 96 are positioned over posts 92 as shownin FIG. 20C and “horizontal” control lines 94 are positioned with theirwide portions between posts 92, as shown in FIG. 20D.

As can be seen in FIG. 20C, when “vertical” control lines 96 arepressurized, the membrane of the integrated structure formed by theelastomeric layer initially positioned between layers 90 and 95 inregions 98 will be deflected downwardly over the array of flow channelssuch that flow in only able to pass in flow direction F2 (i.e.:vertically), as shown.

As can be seen in FIG. 20D, when “horizontal” control lines 94 arepressurized, the membrane of the integrated structure formed by theelastomeric layer initially positioned between layers 90 and 95 inregions 99 will be deflected downwardly over the array of flow channels,(but only in the regions where they are widest), such that flow in onlyable to pass in flow direction F1 (i.e.: horizontally), as shown.

The design illustrated in FIG. 20 allows a switchable flow array to beconstructed from only two elastomeric layers, with no vertical viaspassing between control lines in different elastomeric layers required.If all vertical flow control lines 94 are connected, they may bepressurized from one input. The same is true for all horizontal flowcontrol lines 96.

11. Normally-Closed Valve Structure

FIGS. 7B and 7H above depict a valve structure in which the elastomericmembrane is moveable from a first relaxed position to a second actuatedposition in which the flow channel is blocked. However, the presentinvention is not limited to this particular valve configuration.

FIGS. 21A-21J show a variety of views of a normally-closed valvestructure in which the elastomeric membrane is moveable from a firstrelaxed position blocking a flow channel, to a second actuated positionin which the flow channel is open, utilizing a negative controlpressure.

FIG. 21A shows a plan view, and FIG. 21B shows a cross sectional viewalong line 42B-42B′, of normally-closed valve 4200 in an unactuatedstate. Flow channel 4202 and control channel 4204 are formed inelastomeric block 4206 overlying substrate 4205. Flow channel 4202includes a first portion 4202 a and a second portion 4202 b separated byseparating portion 4208. Control channel 4204 overlies separatingportion 4208. As shown in FIG. 42B, in its relaxed, unactuated position,separating portion 4008 remains positioned between flow channel portions4202 a and 4202 b, interrupting flow channel 4202.

FIG. 21C shows a cross-sectional view of valve 4200 wherein separatingportion 4208 is in an actuated position. When the pressure withincontrol channel 4204 is reduced to below the pressure in the flowchannel (for example by vacuum pump), separating portion 4208experiences an actuating force drawing it into control channel 4204. Asa result of this actuation force membrane 4208 projects into controlchannel 4204, thereby removing the obstacle to a flow of materialthrough flow channel 4202 and creating a passageway 4203. Upon elevationof pressure within control channel 4204, separating portion 4208 willassume its natural position, relaxing back into and obstructing flowchannel 4202.

The behavior of the membrane in response to an actuation force may bechanged by varying the width of the overlying control channel.Accordingly, FIGS. 21D-42H show plan and cross-sectional views of analternative embodiment of a normally-closed valve 4201 in which controlchannel 4207 is substantially wider than separating portion 4208. Asshown in cross-sectional views FIG. 21E-F along line 42E-42E′ of FIG.21D, because a larger area of elastomeric material is required to bemoved during actuation, the actuation force necessary to be applied isreduced.

FIGS. 21G and H show a cross-sectional views along line 40G-40G′ of FIG.21D. In comparison with the unactuated valve configuration shown in FIG.21G, FIG. 21H shows that reduced pressure within wider control channel4207 may under certain circumstances have the unwanted effect of pullingunderlying elastomer 4206 away from substrate 4205, thereby creatingundesirable void 4212.

Accordingly, FIG. 21I shows a plan view, and FIG. 21J shows across-sectional view along line 21I-21J′ of FIG. 211, of valve structure4220 which avoids this problem by featuring control line 4204 with aminimum width except in segment 4204 a overlapping separating portion4208. As shown in FIG. 21J, even under actuated conditions the narrowercross-section of control channel 4204 reduces the attractive force onthe underlying elastomer material 4206, thereby preventing thiselastomer material from being drawn away from substrate 4205 andcreating an undesirable void.

While a normally-closed valve structure actuated in response to pressureis shown in FIGS. 21A-21J, a normally-closed valve in accordance withthe present invention is not limited to this configuration. For example,the separating portion obstructing the flow channel could alternativelybe manipulated by electric or magnetic fields, as described extensivelyabove.

12. Side-Actuated Valve

While the above description has focused upon microfabricated elastomericvalve structures in which a control channel is positioned above andseparated by an intervening elastomeric membrane from an underlying flowchannel, the present invention is not limited to this configuration.FIGS. 22A and 22B show plan views of one embodiment of a side-actuatedvalve structure in accordance with one embodiment of the presentinvention.

FIG. 22A shows side-actuated valve structure 4800 in an unactuatedposition. Flow channel 4802 is formed in elastomeric layer 4804. Controlchannel 4806 abutting flow channel 4802 is also formed in elastomericlayer 4804. Control channel 4806 is separated from flow channel 4802 byelastomeric membrane portion 4808. A second elastomeric layer (notshown) is bonded over bottom elastomeric layer 4804 to enclose flowchannel 4802 and control channel 4806.

FIG. 22B shows side-actuated valve structure 4800 in an actuatedposition. In response to a build up of pressure within control channel4806, membrane 4808 deforms into flow channel 4802, blocking flowchannel 4802. Upon release of pressure within control channel 4806,membrane 4808 would relax back into control channel 4806 and open flowchannel 4802.

While a side-actuated valve structure actuated in response to pressureis shown in FIGS. 22A and 22B, a side-actuated valve in accordance withthe present invention is not limited to this configuration. For example,the elastomeric membrane portion located between the abutting flow andcontrol channels could alternatively be manipulated by electric ormagnetic fields, as described extensively above.

13. Composite Structures

Microfabricated elastomeric structures of the present invention may becombined with non-elastomeric materials to create composite structures.FIG. 23 shows a cross-sectional view of one embodiment of a compositestructure in accordance with the present invention. FIG. 23 showscomposite valve structure 5700 including first, thin elastomer layer5702 overlying semiconductor-type substrate 5704 having channel 5706formed therein. Second, thicker elastomer layer 5708 overlies firstelastomer layer 5702. Actuation of first elastomer layer 5702 to driveit into channel 5706, will cause composite structure 5700 to operate asa valve.

FIG. 24 shows a cross-sectional view of a variation on this theme,wherein thin elastomer layer 5802 is sandwiched between two hard,semiconductor substrates 5804 and 5806, with lower substrate 5804featuring channel 5808. Again, actuation of thin elastomer layer 5802 todrive it into channel 5808 will cause composite structure 5810 tooperate as a valve.

The structures shown in FIG. 23 or 24 may be fabricated utilizing eitherthe multilayer soft lithography or encapsulation techniques describedabove. In the multilayer soft lithography method, the elastomer layer(s)would be formed and then placed over the semiconductor substrate bearingthe channel. In the encapsulation method, the channel would be firstformed in the semiconductor substrate, and then the channel would befilled with a sacrificial material such as photoresist. The elastomerwould then be formed in place over the substrate, with removal of thesacrificial material producing the channel overlaid by the elastomermembrane. As is discussed in detail below in connection with bonding ofelastomer to other types of materials, the encapsulation approach mayresult in a stronger seal between the elastomer membrane component andthe underlying nonelastomer substrate component.

As shown in FIGS. 23 and 24, a composite structure in accordance withembodiments of the present invention may include a hard substrate thatbears a passive feature such as a channels. However, the presentinvention is not limited to this approach, and the underlying hardsubstrate may bear active features that interact with an elastomercomponent bearing a recess. This is shown in FIG. 25, wherein compositestructure 5900 includes elastomer component 5902 containing recess 5904having walls 5906 and ceiling 5908. Ceiling 5908 forms flexible membraneportion 5909. Elastomer component 5902 is sealed against substantiallyplanar nonelastomeric component 5910 that includes active device 5912.Active device 5912 may interact with material present in recess 5904and/or flexible membrane portion 5909.

Many Types of active structures may be present in the nonelastomersubstrate. Active structures that could be present in an underlying hardsubstrate include, but are not limited to, resistors, capacitors,photodiodes, transistors, chemical field effect transistors (chemFET's), amperometric/coulometric electrochemical sensors, fiber optics,fiber optic interconnects, light emitting diodes, laser diodes, verticalcavity surface emitting lasers (VCSEL's), micromirrors, accelerometers,pressure sensors, flow sensors, CMOS imaging arrays, CCD cameras,electronic logic, microprocessors, thermistors, Peltier coolers,waveguides, resistive heaters, chemical sensors, strain gauges,inductors, actuators (including electrostatic, magnetic,electromagnetic, bimetallic, piezoelectric, shape-memory-alloy based,and others), coils, magnets, electromagnets, magnetic sensors (such asthose used in hard drives, superconducting quantum interference devices(SQUIDS) and other types), radio frequency sources and receivers,microwave frequency sources and receivers, sources and receivers forother regions of the electromagnetic spectrum, radioactive particlecounters, and electrometers.

As is well known in the art, a vast variety of technologies can beutilized to fabricate active features in semiconductor and other typesof hard substrates, including but not limited printed circuit board(PCB) technology, CMOS, surface micromachining, bulk micromachining,printable polymer electronics, and TFT and otheramorphous/polycrystalline techniques as are employed to fabricate laptopand flat screen displays.

A variety of approaches can be employed to seal the elastomericstructure against the nonelastomeric substrate, ranging from thecreation of a Van der Waals bond between the elastomeric andnonelastomeric components, to creation of covalent or ionic bondsbetween the elastomeric and nonelastomeric components of the compositestructure. Example approaches to sealing the components together arediscussed below, approximately in order of increasing strength.

A first approach is to rely upon the simple hermetic seal resulting fromVan der Waals bonds formed when a substantially planar elastomer layeris placed into contact with a substantially planar layer of a harder,non-elastomer material. In one embodiment, bonding of RTV elastomer to aglass substrate created a composite structure capable of withstanding upto about 3-4 psi of pressure. This may be sufficient for many potentialapplications.

A second approach is to utilize a liquid layer to assist in bonding. Oneexample of this involves bonding elastomer to a hard glass substrate,wherein a weakly acidic solution (5 μl HCl in H₂O, pH 2) was applied toa glass substrate. The elastomer component was then placed into contactwith the glass substrate, and the composite structure baked at 37° C. toremove the water. This resulted in a bond between elastomer andnon-elastomer able to withstand a pressure of about 20 psi. In thiscase, the acid may neutralize silanol groups present on the glasssurface, permitting the elastomer and non-elastomer to enter into goodVan der Waals contact with each other.

Exposure to ethanol can also cause device components to adhere together.In one embodiment, an RTV elastomer material and a glass substrate werewashed with ethanol and then dried under Nitrogen. The RTV elastomer wasthen placed into contact with the glass and the combination baked for 3hours at 80° C. Optionally, the RTV may also be exposed to a vacuum toremove any air bubbles trapped between the slide and the RTV. Thestrength of the adhesion between elastomer and glass using this methodhas withstood pressures in excess of 35 psi. The adhesion created usingthis method is not permanent, and the elastomer may be peeled off of theglass, washed, and resealed against the glass. This ethanol washingapproach can also be employed used to cause successive layers ofelastomer to bond together with sufficient strength to resist a pressureof 30 psi. In alternative embodiments, chemicals such as other alcoholsor diols could be used to promote adhesion between layers.

An embodiment of a method of promoting adhesion between layers of amicrofabricated structure in accordance with the present inventioncomprises exposing a surface of a first component layer to a chemical,exposing a surface of a second component layer to the chemical, andplacing the surface of the first component layer into contact with thesurface of the second elastomer layer.

A third approach is to create a covalent chemical bond between theelastomer component and functional groups introduced onto the surface ofa nonelastomer component. Examples of derivitization of a nonelastomersubstrate surface to produce such functional groups include exposing aglass substrate to agents such as vinyl silane or aminopropyltriethoxysilane (APTES), which may be useful to allow bonding of the glass tosilicone elastomer and polyurethane elastomer materials, respectively.

A fourth approach is to create a covalent chemical bond between theelastomer component and a functional group native to the surface of thenonelastomer component. For example, RTV elastomer can be created withan excess of vinyl groups on its surface. These vinyl groups can becaused to react with corresponding functional groups present on theexterior of a hard substrate material, for example the Si—H bondsprevalent on the surface of a single crystal silicon substrate afterremoval of native oxide by etching. In this example, the strength of thebond created between the elastomer component and the nonelastomercomponent has been observed to exceed the materials strength of theelastomer components.

14. Cell Pen/Cell Cage

In yet a further application of the present invention, an elastomericstructure can be utilized to manipulate organisms or other biologicalmaterial. FIGS. 26A-26D show plan views of one embodiment of a cell penstructure in accordance with the present invention.

Cell pen array 4400 features an array of orthogonally-oriented flowchannels 4402, with an enlarged “pen” structure 4404 at the intersectionof alternating flow channels. Valve 4406 is positioned at the entranceand exit of each pen structure 4404. Peristaltic pump structures 4408are positioned on each horizontal flow channel and on the vertical flowchannels lacking a cell pen structure.

Cell pen array 4400 of FIG. 26A has been loaded with cells A-H that havebeen previously sorted. FIGS. 26B-26C show the accessing and removal ofindividually stored cell C by 1) opening valves 4406 on either side ofadjacent pens 4404 a and 4404 b, 2) pumping horizontal flow channel 4402a to displace cells C and G, and then 3) pumping vertical flow channel4402 b to remove cell C. FIG. 26D shows that second cell G is moved backinto its prior position in cell pen array 4400 by reversing thedirection of liquid flow through horizontal flow channel 4402 a.

The cell pen array 4404 described above is capable of storing materialswithin a selected, addressable position for ready access. However,living organisms such as cells may require a continuous intake of foodsand expulsion of wastes in order to remain viable. Accordingly, FIGS.27A and 27B show plan and cross-sectional views (along line 45B-45B′)respectively, of one embodiment of a cell cage structure in accordancewith the present invention.

Cell cage 4500 is formed as an enlarged portion 4500 a of a flow channel4501 in an elastomeric block 4503 in contact with substrate 4505. Cellcage 4500 is similar to an individual cell pen as described above inFIGS. 26A-26D, except that ends 4500 b and 4500 c of cell cage 4500 donot completely enclose interior region 4500 a. Rather, ends 4500 a and4500 b of cage 4500 are formed by a plurality of retractable pillars4502. Pillars 4502 may be part of a membrane structure of anormally-closed valve structure as described extensively above inconnection with FIGS. 21A-21J.

Specifically, control channel 4504 overlies pillars 4502. When thepressure in control channel 4504 is reduced, elastomeric pillars 4502are drawn upward into control channel 4504, thereby opening end 4500 bof cell cage 4500 and permitting a cell to enter. Upon elevation ofpressure in control channel 4504, pillars 4502 relax downward againstsubstrate 4505 and prevent a cell from exiting cage 4500.

Elastomeric pillars 4502 are of a sufficient size and number to preventmovement of a cell out of cage 4500, but also include gaps 4508 whichallow the flow of nutrients into cage interior 4500 a in order tosustain cell(s) stored therein. Pillars 4502 on opposite end 4500 c aresimilarly configured beneath second control channel 4506 to permitopening of the cage and removal of the cell as desired.

The cross-flow channel architecture illustrated shown in FIGS. 26A-26Dcan be used to perform functions other than the cell pen just described.For example, the cross-flow channel architecture can be utilized inmixing applications.

This is shown in FIGS. 28A-B, which illustrate a plan view of mixingsteps performed by a microfabricated structure in accordance anotherembodiment of the present invention. Specifically, portion 7400 of amicrofabricated mixing structure comprises first flow channel 7402orthogonal to and intersecting with second flow channel 7404. Controlchannels 7406 overlie flow channels 7402 and 7404 and form valve pairs7408 a-b and 7408 c-d that surround each intersection 7412.

As shown in FIG. 28A, valve pair 7408 a-b is initially opened whilevalve pair 7408 c-d is closed, and fluid sample 7410 is flowed tointersection 7412 through flow channel 7402. Valve pair 7408 c-d is thenactuated, trapping fluid sample 7410 at intersection 7412.

Next, as shown in FIG. 28B, valve pairs 7408 a-b and 7408 c-d areopened, such that fluid sample 7410 is injected from intersection 7412into flow channel 7404 bearing a cross-flow of fluid. The process shownin FIGS. 28A-B can be repeated to accurately dispense any number offluid samples down cross-flow channel 7404.

While the embodiment shown and described above in connection with FIGS.28A-28B utilizes linked valve pairs on opposite sides of the flowchannel intersections, this is not required by the present invention.Other configurations, including linking of adjacent valves of anintersection, or independent actuation of each valve surrounding anintersection, are possible to provide the desired flow characteristics.With the independent valve actuation approach however, it should berecognized that separate control structures would be utilized for eachvalve, complicating device layout.

15. Metering by Volume Exclusion

Many high throughput screening and diagnostic applications call foraccurate combination and of different reagents in a reaction chamber.Given that it is frequently necessary to prime the channels of amicrofluidic device in order to ensure fluid flow, it may be difficultto ensure mixed solutions do not become diluted or contaminated by thecontents of the reaction chamber prior to sample introduction.

Volume exclusion is one technique enabling precise metering of theintroduction of fluids into a reaction chamber. In this approach, areaction chamber may be completely or partially emptied prior to sampleinjection. This method reduces contamination from residual contents ofthe chamber contents, and may be used to accurately meter theintroduction of solutions in a reaction chamber.

Specifically, FIGS. 29A-29D show cross-sectional views of a reactionchamber in which volume exclusion is employed to meter reactants. FIG.29A shows a cross-sectional view of portion 6300 of a microfluidicdevice comprising first elastomer layer 6302 overlying second elastomerlayer 6304. First elastomer layer 6302 includes control chamber 6306 influid communication with a control channel (not shown). Control chamber6306 overlies and is separated from dead-end reaction chamber 6308 ofsecond elastomer layer 6304 by membrane 6310. Second elastomer layer6304 further comprises flow channel 6312 leading to dead-end reactionchamber 6308.

FIG. 29B shows the result of a pressure increase within control chamber6306. Specifically, increased control chamber pressure causes membrane6310 to flex downward into reaction chamber 6308, reducing by volume Vthe effective volume of reaction chamber 6308. This in turn excludes anequivalent volume V of reactant from reaction chamber 6308, such thatvolume V of first reactant X is output from flow channel 6312. The exactcorrelation between a pressure increase in control chamber 6306 and thevolume of material output from flow channel 6312 can be preciselycalibrated.

As shown in FIG. 29C, while elevated pressure is maintained withincontrol chamber 6306, volume V′ of second reactant Y is placed intocontact with flow channel 6312 and reaction chamber 6308.

In the next step shown in FIG. 29D, pressure within control chamber 6306is reduced to original levels. As a result, membrane 6310 relaxes andthe effective volume of reaction chamber 6308 increases. Volume V ofsecond reactant Y is sucked into the device. By varying the relativesize of the reaction and control chambers, it is possible to accuratelymix solutions at a specified relative concentration. It is worth notingthat the amount of the second reactant Y that is sucked into the deviceis solely dependent upon the excluded volume V, and is independent ofvolume V′ of Y made available at the opening of the flow channel.

While FIGS. 29A-29D show a simple embodiment of the present inventioninvolving a single reaction chamber, in more complex embodimentsparallel structures of hundreds or thousands of reaction chambers couldbe actuated by a pressure increase in a single control line.

Moreover, while the above description illustrates two reactants beingcombined at a relative concentration that fixed by the size of thecontrol and reaction chambers, a volume exclusion technique could beemployed to combine several reagents at variable concentrations in asingle reaction chamber. One possible approach is to use several,separately addressable control chambers above each reaction chamber. Anexample of this architecture would be to have ten separate control linesinstead of a single control chamber, allowing ten equivalent volumes tobe pushed out or sucked in.

Another possible approach would utilize a single control chamberoverlying the entire reaction chamber, with the effective volume of thereaction chamber modulated by varying the control chamber pressure. Inthis manner, analog control over the effective volume of the reactionchamber is possible. Analog volume control would in turn permit thecombination of many solutions reactants at arbitrary relativeconcentrations.

An embodiment of a method of metering a volume of fluid in accordancewith the present invention comprises providing a chamber having a volumein an elastomeric block separated from a control recess by anelastomeric membrane, and supplying a pressure to the control recesssuch that the membrane is deflected into the chamber and the volume isreduced by a calibrated amount, thereby excluding from the chamber thecalibrated volume of fluid.

II. Electrostatic/Electrostrictive Actuation

An embodiment of a valve structure in accordance with the presentinvention comprises an elastomeric block formed with first and secondmicrofabricated recesses separated by a membrane portion of theelastomeric block. The valve is actuated by positioning a compliantelectrode on a first side of the first recess proximate to and inphysical communication with the membrane.

Where the valve is to be electrostatically actuated, a second electrodeis positioned on a second side of the first recess opposite the firstside. Application of a potential difference across the electrodes causesthe compliant electrode and the membrane to be attracted into the flowchannel.

Where the valve is to be electrostrictively actuated, a second electrodeis positioned on the same side of the recess as the compliant electrode.Application of a potential difference across the electrodes causes theelectrodes to be attracted such that elastomer material between them iscompressed and bows into the flow channel.

1. Electrostatic Actuation

FIG. 30A shows a simplified cross-sectional view of one embodiment of anelectrostatically actuated valve structure in accordance with thepresent invention in a nonactuated state. Valve structure 6400 comprisescontrol recess 6402 positioned in elastomer material 6403 and orientedorthogonal relative to underlying flow channel 6404. Control recess 6402is separated from flow channel 6404 by elastomer membrane 6406 formedfrom the same elastomeric material 6403 in which control recess 6402 iscreated. Floor 6404 a of flow channel 6404 is formed from an underlyingsubstrate 6408. The surface of substrate 6408 bears electrode 6410.Compliant electrode 6412 is positioned within elastomer 6403 over firstelectrode 6410.

FIG. 30B shows a simplified cross-sectional view of the valve structureof FIG. 30A in its actuated state. As shown in FIG. 30B, duringoperation of valve structure 6400, application of a potential differencebetween electrode 6410 and compliant electrode 6412 across flow channel6404 causes compliant electrode 6412 to be attracted to electrode 6410.As a result of this attractive force, compliant electrode 6412 andassociated membrane portion 6406 are drawn into flow channel 6404.Cessation of a potential difference between electrodes 6410 and 6412terminates the attractive force, and membrane portion 6406 and compliantelectrode 6412 resume their original positions such that flow channel6404 is no longer obstructed.

In alternative embodiments in accordance with the present invention,electrically conducting fluids disposed in the control channel may serveas compliant electrodes. This is illustrated in FIGS. 31A-B, which showcross-sectional views of an alternative embodiment of anelectrostatically actuated valve structure in nonactuated and actuatedstates, respectively. The valve structure of FIG. 31A is similar to thatof FIGS. 30A-B, except that recess channel 6502 is filled with anelectrically-conducting fluid 6505. Examples of suchelectrically-conducting fluids include but are not limited to colloidalsuspensions of conducting particles, ionic solutions, liquid metals, andsolutions of conductive polymers. The electrically-conducting fluidwithin control recess 6502 serves as the compliant electrode structure,such that the electrostatic attraction arising from application of apotential difference between electrode 6510 and the contents of controlrecess 6502 draws membrane 6506 into flow channel 6504.

While the embodiments of a valve structure described above in connectionwith FIGS. 30A-B and 31A-B utilize a lower electrode positioned at thesurface of the underlying substrate to accomplish electrostaticactuation, this is not required by the present invention. For example,FIG. 32A shows a simplified cross-sectional view of an alternativeembodiment of a valve structure in a nonactuated state. FIG. 32B shows asimplified cross-sectional view of the embodiment of the valve structureof FIG. 32A in an actuated state.

Valve structure 6600 of FIGS. 32A-B resembles valve structure 6600 ofFIGS. 31A-B, except that lower electrode 6610 is embedded at a depthwithin substrate 6608 rather than at its surface. This orientation ofthe lower electrode 6610 allows an electric field resulting fromapplication of a potential difference between electrodes 6610 and 6612to attract overlying compliant electrode 6612 and associated elastomericmembrane 6606 for actuation purposes, but prevents lower electrode 6610from directly contacting the contents of flow channel 6604.

The embedded configuration just described is useful in applicationswhere electrode 6610 may undesirably corrode or otherwise react with thecontents of the flow channel. It is also useful in embodiments whereinthe overlying compliant electrode is located on the ceiling of the flowchannel directly beneath the membrane. In such an embodiment, theembedded bottom electrode is prevented from shorting with the uppercompliant electrode through direct contact or arcing. However, it is tobe understood that embodiments of a valve structure wherein both thecompliant electrode and the lower electrode are directly in contact withthe flow channel, also fall within the scope of the instant invention.

FIG. 33A shows a simplified cross-sectional view of yet anotherembodiment of an electrostatically actuated valve structure in anonactuated state. FIG. 33B shows a simplified cross-sectional view ofone embodiment of the valve structure of FIG. 33A in an actuated state.Valve structure 6700 is similar to the valve structure of FIGS. 32A-B,except that upper compliant electrode 6712 is positioned on the lowersurface of membrane 6706 separating control recess 6702 from flowchannel 6704. Application of a potential difference between compliantelectrode 6712 and lower electrode 6710 across flow channel 6704 drawscompliant electrode 6712 and associated membrane 6706 into the flowchannel as indicated in FIG. 33B.

While the above description has focused upon the electrostatic actuationof a valve structure, the present invention is not limited to actuationof this particular structure. For example, the '025 applicationdescribes in detail the fabrication of peristaltic pumps, sorters,multiplexers, and other fluid handing structures that could also beactuated by a compliant electrode in accordance with embodiments of thepresent invention. Moreover, the application of compliantelectrostatically actuated electrodes is not limited to fluid handlingapplications. For example, the '025 application describes a number ofnon-fluidic structures including optical devices such as micromirrorarrays and refractive lenses.

While the above embodiments illustrate direct actuation of a valvethrough electrostatic actuation, the present invention is not limited tothis mechanism. In an alternative embodiment, a flow channel proximateto an electrostatically-actuated membrane could function as a controlchannel of a second valve. In a manner analogous to the operation of abellows, electrostatic actuation of the membrane could change thepressure within the flow channel. Where this flow channel serves as thecontrol channel for a second valve, the membrane of the second valvewould in turn be actuated by a pressure differential in the controlchannel.

While the above embodiments illustrate valve structures that include asingle compliant electrode, a valve structure could utilize a compliantmaterial for both electrode structures. Of course, the degree ofmovement of each compliant electrode in response to an electric fieldwould vary according to the mass and flexibility of the associatedmaterial. Thus where a compliant electrode is deeply embedded in aflexible substrate, or is present within in a rigid substrate, theamount of flexion of the second compliant electrode would be relativelysmall compared with that of the first compliant electrode that isassociated with the membrane.

2. Electrostrictive Actuation

FIG. 34A shows a simplified cross-sectional view of one embodiment of anelectrostrictively actuated valve structure in accordance with thepresent invention in a nonactuated state. Valve structure 6800 issimilar to the valve structure of prior FIGS. 30A-B, except that therole of the channels is reversed. Specifically, valve structure 6800comprises flow channel 6802 positioned in elastomer material 6803 aboveunderlying control recess 6804. Flow channel 6802 is separated fromcontrol recess 6804 by elastomer membrane 6806 formed from the sameelastomeric material 6803 in which flow channel 6802 is created. Firstcompliant electrode 6810 is formed on one side of membrane 6806proximate to flow channel 6802, and second compliant electrode 6812 isformed on the opposite side of membrane 6806 proximate to control recess6804.

FIG. 34B shows a simplified cross-sectional view of the valve structureof FIG. 34A in its actuated state. As shown in FIG. 34B, duringoperation of valve structure 6800, application of a potential differencebetween first compliant electrode 6810 and second compliant electrode6812 causes attraction between first compliant electrode 6812 and secondcompliant electrode 6810. As a result of this attractive force, theelastomer material making up membrane 6806 is compressed.

Compression of elastomer material between the electrodes results inlateral displacement of elastomeric material therebetween, causingmembrane 6806 to be reduced in thickness and to bow upward in conformitywith the existing arched profile of control recess 6804. Aselectrostrictively actuated in this matter, bowed membrane 6806eventually projects into flow channel 6802, blocking it. Where materialsare flowed through flow channel 6802, the electrostrictive actuationmethod just described can be utilized to control this flow.

As with the electrostatically actuated valves described above,alternative embodiments of electrostrictively-actuated valves inaccordance with the present invention may utilize electricallyconducting fluids as compliant electrodes. This is illustrated in FIGS.35A-B, which show cross-sectional views of an alternative embodiment ofan electrostrictively-actuated valve structure in nonactuated andactuated states, respectively. Valve structure 6900 of FIG. 35A issimilar to that of FIGS. 34A-B, except that the second compliantelectrode is electrically conducting fluid 6905 present in controlrecess 6904. Examples of such electrically-conducting fluids include butare not limited to colloidal suspensions of conducting particles, ionicsolutions, liquid metals, and solutions of conductive polymers. Theelectrically-conducting fluid within control recess 6904 serves as thesecond compliant electrode, such that the electrostatic attractionarising from application of a potential difference between firstcompliant electrode 6910 and the contents of control recess 6904 createsan electrostrictive force that compresses the elastomer material betweenthe compliant electrodes. This compression force causes membrane 6906 tobow upward in conformity with the existing arch shape of control recess6904, eventually projecting into and closing flow channel 6902.

While the embodiments of an electrostrictively-actuated valve structuredescribed above in connection with FIGS. 34A-B and 35A-B utilize acompliant electrode positioned at the arched base of the membrane incontact with the flow channel, this is not required by the presentinvention. For example, FIG. 36A shows a simplified cross-sectional viewof an alternative embodiment of an electrostrictively-actuated valvestructure in a nonactuated state. FIG. 36B shows a simplifiedcross-sectional view of the embodiment of the valve structure of FIG.36A in an actuated state.

Valve structure 7000 of FIGS. 36A-B resembles the valve structure ofFIGS. 34A-B, except that upper compliant electrode 7010 is embedded at adepth within membrane 7006 rather than at its upper surface. Thisorientation of the upper compliant electrode 7010 allows an electricfield resulting from application of a potential difference betweencompliant electrodes 7010 and 7012 to attract underlying compliantelectrode 7012 and thereby compress the intervening elastomeric membrane7006 for purposes of electrostrictive actuation, but prevents compliantupper electrode 7010 from directly contacting the contents of flowchannel 7002. The embedded configuration just described is useful inapplications where compliant electrode 7010 may undesirably corrode orotherwise react with the contents of the flow channel.

While the above description has focused upon the electrostrictiveactuation of a valve structure for microfluidics applications, thepresent invention is not limited to actuation of this particularstructure. For example, the '025 application describes in detail thefabrication of peristaltic pumps, sorters, multiplexers, and other fluidhanding structures that could also be actuated by compliant electrodesin accordance with embodiments of the present invention. Moreover, theapplication of compliant electrostrictively actuated electrodes is notlimited to fluid handling applications. For example, the '025application describes a number of non-fluidic structures includingoptical devices such as micromirror arrays and refractive lenses.

While the above embodiments illustrate direct actuation of a valvethrough electrostrictive actuation, the present invention is not limitedto this mechanism. In an alternative embodiment, a flow channelproximate to an electrostrictively-actuated membrane could function as acontrol channel of a second valve. In a manner analogous to theoperation of a bellows, electrostrictive actuation of the membrane couldchange the pressure within the flow channel. Where this flow channelserves as the control channel for a second valve, the membrane of thesecond valve would in turn be actuated by a pressure differential in thecontrol channel.

It is also important to recognize that the degree of movement of eachcompliant electrode in response to an electric field, and hence theelectrostrictive actuation force, would vary according to the characterof materials forming the electrode and the associated membrane material.

3. Fabrication Materials and Techniques

The valve structure shown above may be fabricated according to a numberof different methods. As described in detail in the '025 application,one fabrication approach utilizes soft lithography, wherein conventionalsemiconductor lithographic techniques are employed to pattern raisedfeatures on a silicon substrate. Subsequent formation of an elastomerlayer over the raised features, followed by removal of the elastomer,results in the formation of channels and recesses in the elastomer.Successive elastomer layers patterned in this manner can be bondedtogether to form multilayered structures.

An alternative fabrication method taught by the '025 applicationinvolves the direct patterning of elastomer materials utilizingphotolithographic techniques. Channels and recesses formed in theelastomer thereby are then filled with a sacrificial material such asphotoresist. Subsequent formation of additional successive elastomerlayers over the sacrificial features, followed by removal of sacrificialmaterial entrapped therein (i.e. by exposure to developer), results information of valve structures. Fabrication of valve structures utilizingentrapment of sacrificial materials is described in greater detail inthe '025 application.

The electrostatically actuated and electrostrictively actuated valvestructures shown above may be fabricated from a variety of combinationsof materials. A brief description of the most common classes ofelastomer materials has been presented previously.

Compliant electrodes utilized for actuation of valve structures inaccordance with embodiments of the present invention may also be formedfrom a variety of materials. Published PCT applications WO 01/06579 andWO 01/06575 are incorporated by reference herein for all purposes. Thesepublished PCT applications disclose compliant electrode materials,compliant electrode structures, and methods of fabricating compliantelectrodes suitable for use in embodiments in accordance with thepresent invention.

In one embodiment of the present invention, compliant electrodes may beformed by pattering less-compliant conductive materials to allowflexibility (for instance gold or aluminum). In an alternativeembodiment, compliant electrodes may be formed by disposing electricallyconducting fluids within a recess or channel. Examples ofelectrically-conducting fluids which may serve as compliant electrodesin accordance with embodiments of the present invention include but arenot limited to colloidal suspensions of conducting particles, ionicsolutions, liquid metals, and solutions of conductive polymers.

In other alternative embodiments, the compliant electrodes may be formedfrom electroactive polymers. Examples of suitable electroactive polymersthat may serve as compliant electrodes include, but are not limited to,NuSil CF19-2186 from NuSil Technology of Carpenteria, Calif., HS3silicone and 730 fluorosilicone from Dow Corning of Wilmington, Del.,and 4900 VHB acrylic polymer from 3M Corp. of St. Paul, Minn.

In still other alternative embodiments in accordance with the presentinvention, compliant electrodes may be formed from elastomer materialsfeaturing electrically conducting species doped or otherwise introducedto impart conductive activity. In general, elastomers described asappropriate for forming structures as described in the '025 patent willalso be suitable for the formation of electrostatic actuators, andexamples of suitable elastomer materials include, but are not limitedto, GE RTV 615 silicone, Sylgard 182, 184 or 186, or aliphatic urethanediacrylates such as (but not limited to) Ebecryl 270 or Irr 245 from UCBChemical.

Introduction of conductive species into the polymer of the compliantelectrodes could be accomplished in a number of ways. In accordance withone embodiment of the present invention, conductive metals including butnot limited to Au, Ag, Al, Cu, or W can be mixed with the elastomer,deposited or plated onto, or implanted into, a surface of the elastomer.In accordance with other embodiments, conductive greases includingcolloidal sized conductive particles can be mixed in binder such assilicone that cures to form a conductive semi-solid.

In other embodiments, carbon may be used as the conductive material. Forexample, thin layers of carbon fibrils or carbon nanotubules may beapplied to impart conductivity. Other examples of carbon-based materialsfor imparting electrical conductivity include carbon black, graphite,and suspensions or solutions of carbon.

Other, ionically conductive materials may alternatively be introduced tocreate a compliant electrode, for example in water-based polymermaterials such as glycerol or salt in gelatin, iodine-doped naturalrubbers and water based emulsions to which organic salts such aspotassium iodide have been added. For hydrophobic polymers that may notadhere to a water-based dopant, the surface of the polymer may bepretreated by plasma etching or with a fine powder such as graphite orcarbon black to increase adherence. The various materials describedabove may also be mixed in droplets from a spray in order to enhanceadhesion or other desirable properties.

While the present invention has been described herein with reference toparticular embodiments thereof, a latitude of modification, variouschanges and substitutions are intended in the foregoing disclosure, andit will be appreciated that in some instances some features of theinvention will be employed without a corresponding use of other featureswithout departing from the scope of the invention as set forth.Therefore, many modifications may be made to adapt a particularsituation or material to the teachings of the invention withoutdeparting from the essential scope and spirit of the present invention.It is intended that the invention not be limited to the particularembodiment disclosed as the best mode contemplated for carrying out thisinvention, but that the invention will include all embodiments andequivalents falling within the scope of the claims.

1. A method of actuating an elastomeric structure comprising: applying apotential difference between a compliant electrode and a secondelectrode positioned on opposite sides of a first microfabricated recessof an elastomeric block, such that the compliant electrode is attractedto the second electrode and an associated elastomeric membraneseparating the first microfabricated recess from a secondmicrofabricated recess is drawn into the first recess.
 2. The method ofclaim 1 wherein the potential difference is applied between the secondelectrode and an electrically conducting fluid disposed in the secondmicrofabricated recess.
 3. The method of claim 1 wherein the potentialdifference is applied between the second electrode and a compliantelectrode comprising an electroactive polymer.
 4. A method ofcontrolling a flow of material in an elastomeric structure comprisingapplying a potential difference to cause electrostatic actuation of acompliant electrode.
 5. The method of claim 4 wherein the flow occursthrough a microfluidic channel.
 6. The method of claim 1 wherein: thecompliant electrode comprises a first compliant electrode and the secondelectrode comprises a second compliant electrode; and the elastomericmembrane is compressed by attraction of the first compliant electrode tothe second compliant electrode, causing the elastomeric membrane to bowupward into the first microfabricated recess.
 7. The method of claim 6wherein the potential difference is applied between the first compliantelectrode and an electrically conducting fluid disposed in the secondmicrofabricated recess.
 8. The method of claim 6 wherein the potentialdifference is applied between the first compliant electrode comprising afirst electroactive polymer and the second compliant electrodecomprising a second electroactive polymer.
 9. The method of claim 8wherein the first and second electroactive polymers are the samematerial.